Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

Uzu, Miaki; Sato, Hiromi; R, Yamada; Kashiba, Tatsuro; Shibata, Yukihiro; Yamaura, Katsunori; Ueno, Koichi

doi:10.1016/j.jphs.2015.04.002

Cited by 20 publications

(16 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…What is more, Cx43 is proved to be a chemotherapy and radiotherapy sensitizer in multiple cancers through GJIC (Gap Junction Intercellular Communication) dependent or independent manner. 31,32 These findings are greatly in accordance with the increasing evidence. [33][34][35] Since Cx43 suppresses breast cancer cell growth and miR-218-5p suppresses the expression of Cx43, we assumed that miR-218-5p promoted breast cancer cell growth.…”

Section: Discussionsupporting

confidence: 89%

<p>The Multifunction Of miR-218-5p-Cx43 Axis In Breast Cancer</p>

Chen¹,

Jiang²,

Ye³

et al. 2019

OTT

View full text Add to dashboard Cite

Background: Gemcitabine is proven to be the first-line standard treatment of breast cancers. Yet, little is known involving gemcitabine resistance and remains largely to be elucidated. Materials and methods: We evaluated the expression of Cx43 in gemcitabine-resistant cells and parental cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Dual-luciferase reporter assay was applied to examine the epigenetic regulator of Cx43. The role of miR-218-5p-Cx43 axis on cell cytotoxicity, cell proliferation, colony formation, chemoresistance and migration was detected via mammalian expression vector and small short RNA (shRNA) transfection in vitro. Results: In this study, we found that Cx43 expression levels were significantly lower in gemcitabine-resistant cells than in the parental cells. On deep investigation of the epigenetic regulation of Cx43, a few miRNA candidates targeting Cx43 were derived. Through dual-luciferase reporter assay, Cx43 was proved to be a direct target of miR-218-5p. Besides, qPCR, Western blot demonstrated an inverse correlation between miR-218-5p and Cx43 expression in breast cancer cells, thus forming the miR-218-5p-Cx43 axis. Notably, miR-218-5p-Cx43 axis was found to be involved in the process of gemcitabine chemoresistance, cell proliferation and migration in breast cancer cells. Conclusion: Our findings suggested that miR-218-5p-Cx43 axis was versatile and indicated significant potency in breast cancer cells. More importantly, miR-218-5p-Cx43 axis might be valuable in translational medicine, with therapeutic and prognostic information.

show abstract

Section: Discussionsupporting

confidence: 89%

<p>The Multifunction Of miR-218-5p-Cx43 Axis In Breast Cancer</p>

Chen¹,

Jiang²,

Ye³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…Recent molecular biological studies have revealed that esophageal cancer is caused by the accumulation of multiple genetic defects in dominant oncogenes and tumor suppressor genes. In order to elucidate the role of connexin 43 (Cx43) in ESCC, the expression status of Cx43 in patients with ESCC was evaluated (1)(2)(3)(4)(5)(6)(7). In addition, the associations between Cx43 expression and clinicopathological characteristics or prognosis were analyzed.…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 expression is associated with poor survival in patients with esophageal squamous cell carcinoma

Tanaka

Kimura

Ishiguro

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Connexin 43 (Cx43) is an important gap junction protein in vertebrates, which has been reported to function as a tumor suppressor in a number of organs. However, the mechanism underlying the effect of Cx43 on tumor progression remains unknown, with only a limited number of studies reporting on the role of Cx43 in esophageal cancer. In the present study, Cx43 expression was analyzed by immunohistochemical staining and the associations between Cx43 expression and clinicopathological characteristics or prognosis were evaluated. Cx43 was expressed at a high frequency in patients with esophageal squamous cell carcinoma (ESCC). Of the 98 ESCC cases investigated, positivity for Cx43 was observed in 62 cases (63.26%). In patients with high Cx43 expression, the survival rates were significantly reduced compared with those in patients with low Cx43 expression. Moreover, the overexpression of Cx43, as measured by immunohistochemistry, was an independent prognostic indicator of ESCC. Thus, our data indicated that Cx43 may be a candidate molecular prognostic marker and molecular target for the development of an effective therapeutic intervention for patients with esophageal cancer.

show abstract

“…Increasing level of Cx43 in malignant mesothelioma cell enhances sensitivity against cisplatin and sunitinib treatment [11], [12], [13],…”

Section: Mesothelioma-mesotheliomamentioning

confidence: 99%

“…The pivotal role of Cx43 in promoting tumor progression has been previously overlooked because downregulation of Cx43-mediated intercellular communication is normally associated with increased malignancy in tumor cells (5,6). Indeed, for a long period, it was believed that the GJ formed by Cx43 has mostly tumor suppressive effects (5)(6)(7), such as its role in anti-proliferation (8,9), anti-metastasis (10), and pro-apoptosis (11)(12)(13)(14)(15). In contrast, emerging evidence indicates that Cx43 serves a facilitative role in tumorigenesis (5,16), especially in advanced stages (7).…”

Section: Introductionmentioning

confidence: 99%